Drosophila melanogaster is a good model system to study succinate dehydrogenase (SDH) deficiency disease since there are well characterized mutations in the majority of genes that encode for the Drosophila SDH subunits. Mutations in dSdhA are used as models of Leigh Syndrome in flies, and have comparable neurological consequences to those described in patients. Also, mutations in dSdhB and dSdhC result in increased levels of reactive oxygen species and an early onset of mortality and age-related behavioral decay. Molecular genetic analysis in D. melanogaster provides unique approaches to uncover the basic mechanism of action of potential treatments. In this context, we have preliminary data indicating that SDH activity is increased in the mitochondria of flies that were fed the drug rapamycin. Rapamycin is currently being used in organ transplant patients to prevent rejection. Research using experimental animals also suggests that rapamycin has anti- carcinogenic and pro-longevity characteristics. Based on our observations and the documented effects of rapamycin in this proposal we will test the hypothesis that rapamycin can protect from the pathology induced by SDH deficiency, using D. melanogaster as a genetic model.